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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/28719799/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-a-new-player-in-endoplasmic-reticulum-diseases-structure-biology-and-therapeutic-roles
#1
REVIEW
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28719798/chimeric-antigen-receptor-t-cells-for-b-cell-malignancies
#2
REVIEW
Eben I Lichtman, Gianpietro Dotti
The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28686852/integrated-meta-omic-analyses-of-the-gastrointestinal-tract-microbiome-in-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#3
Anne Kaysen, Anna Heintz-Buschart, Emilie E L Muller, Shaman Narayanasamy, Linda Wampach, Cédric C Laczny, Norbert Graf, Arne Simon, Katharina Franke, Jörg Bittenbring, Paul Wilmes, Jochen G Schneider
In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes, during allo-HSCT, and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies...
June 20, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28688236/antigen-specific-regulatory-t-cells-are-police-cars-the-answer
#4
REVIEW
Nicholas A J Dawson, Megan K Levings
Cellular therapy with T-regulatory cells (Tregs) is a promising strategy to control immune responses and restore immune tolerance in a variety of immune-mediated diseases, such as transplant rejection and autoimmunity. Multiple clinical trials are currently testing this approach, typically by infusing a single dose of polyclonal Tregs that have been expanded in vitro. However, evidence from animal models of Treg therapy has clearly shown that antigen-specific Tregs are vastly superior to polyclonal cells, meaning that fewer cells are needed for the desired therapeutic effect...
June 19, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28683259/rna-seq-analysis-of-peripheral-blood-mononuclear-cells-reveals-unique-transcriptional-signatures-associated-with-disease-progression-in-dengue-patients
#5
Arup Banerjee, Shweta Shukla, Abhay Deep Pandey, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Shukla Das, Arjun Malhotra, Amitesh Agarwal, Srima Adhikari, Mehebubar Rahman, Shatakshee Chatterjee, Nemai Bhattacharya, Nandita Basu, Priyanka Pandey, Vikas Sood, Sudhanshu Vrati
Patients infected with Dengue virus usually present a mild, self-limiting febrile dengue infection (DI) that occasionally leads to a potentially lethal complication, called the severe dengue (DS). The ability to identify the prognostic markers of DS could allow an improved disease intervention and management. To identify the transcriptional signatures associated with the dengue disease progression, we carried out the high-throughput sequencing of the RNA isolated from the peripheral blood mononuclear cells (PBMCs) of the dengue patients of varying severity and compared with that in the patients with other febrile illnesses (OFIs) or the healthy controls...
June 17, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28675806/the-future-perspective-metabolomics-in-laboratory-medicine-for-inborn-errors-of-metabolism
#6
REVIEW
Yana Sandlers
Metabolomics can be described as a simultaneous and comprehensive analysis of small molecules in a biological sample. Recent technological and bioinformatics advances have facilitated large-scale metabolomic studies in many areas, including inborn errors of metabolism (IEMs). Despite significant improvements in the diagnosis and treatment of some IEMs, it is still challenging to understand how genetic variation affects disease progression and susceptibility. In addition, a search for new more personalized therapies and a growing demand for tools to monitor the long-term metabolic effects of existing therapies set the stage for metabolomics integration in preclinical and clinical studies...
June 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28668522/the-traumatic-bone-trauma-induced-heterotopic-ossification
#7
REVIEW
Devaveena Dey, Benjamin M Wheatley, David Cholok, Shailesh Agarwal, Paul B Yu, Benjamin Levi, Thomas A Davis
Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence...
June 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28668521/lipidomics-in-translational-research-and-the-clinical-significance-of-lipid-based-biomarkers
#8
REVIEW
Daniel J Stephenson, L Alexis Hoeferlin, Charles E Chalfant
Lipidomics is a rapidly developing field of study that focuses on the identification and quantitation of various lipid species in the lipidome. Lipidomics has now emerged in the forefront of scientific research due to the importance of lipids in metabolism, cancer, and disease. Using both targeted and untargeted mass spectrometry as a tool for analysis, progress in the field has rapidly progressed in the last decade. Having the ability to assess these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and the identification of lipid-based biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia...
June 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651075/modulation-of-natriuretic-peptide-receptors-in-human-adipose-tissue-molecular-mechanisms-behind-the-natriuretic-handicap-in-morbidly-obese-patients
#9
Alessandra Gentili, Maria Rosaria Frangione, Elisa Albini, Carmine Vacca, Maria Anastasia Ricci, Stefano De Vuono, Marcello Boni, Fabio Rondelli, Luciana Rotelli, Graziana Lupattelli, Ciriana Orabona
The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as "natriuretic handicap." Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap. The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28648487/development-of-novel-avenues-to-overcome-challenges-facing-car-t-cells
#10
REVIEW
Soyeon Kim, Edmund K Moon
There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#11
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and natural killer T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651073/hemophilia-a-inhibitor-treatment-the-promise-of-engineered-t-cell-therapy
#12
REVIEW
Kalpana Parvathaneni, Maha Abdeladhim, Kathleen P Pratt, David W Scott
Hemophilia A is a bleeding disorder caused by mutations in the gene encoding factor VIII (FVIII), a cofactor protein that is essential for normal blood clotting. Approximately, 1 in 3 patients with severe hemophilia A produce neutralizing antibodies (inhibitors) that block its biologic function in the clotting cascade. Current efforts to eliminate inhibitors consist of repeated FVIII injections under what is termed an "ITI" protocol (Immune Tolerance Induction). However, this method is extremely costly and approximately 30% of patients undergoing ITI do not achieve peripheral tolerance...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#13
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28641075/postconditioning-with-intralipid-emulsion-protects-against-reperfusion-injury-in-postinfarct-remodeled-rat-hearts-by-activation-of-ros-akt-erk-signaling
#14
Michael Zaugg, Phing-How Lou, Eliana Lucchinetti, Manoj Gandhi, Alexander S Clanachan
The clinically used lipid emulsion Intralipid (ILE) reduces ischemia reperfusion injury in healthy rodent hearts. We tested whether ILE is cardioprotective in postinfarct remodeled hearts. Postinfarct remodeled and sham Sprague-Dawley rat hearts were perfused in working mode and subjected to ischemia (15 minutes) and reperfusion (30 minutes). Left ventricular (LV) work was measured in hearts that were untreated or that received ILE (1%) postconditioning administered at the onset of reperfusion, or the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)-glycine (10 μM) alone or in combination with ILE...
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#15
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28586635/tin-protoporphyrin-activates-the-oxidant-dependent-nrf2-cytoprotective-pathway-and-mitigates-acute-kidney-injury
#16
Ali C M Johnson, Jeff J Delrow, Richard A Zager
Tin protoporphyrin (SnPP), a heme oxygenase (HO) inhibitor, can paradoxically protect against diverse forms of acute kidney injury (AKI). This study sought potential underlying mechanisms. CD-1 mice received intravenous SnPP, followed 4-18 hours later by a variety of renal biochemical, histologic, and genomic assessments. Renal resistance to ischemic-reperfusion injury (IRI) was also sought. SnPP was rapidly taken up by kidney and was confined to proximal tubules. Transient suppression of renal heme synthesis (decreased δ aminolevulinic acid synthase expression), a 2...
May 19, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28583767/lxr-dependent-regulation-of-macrophage-specific-reverse-cholesterol-transport-is-impaired-in-a-model-of-genetic-diabesity
#17
Teresa L Errico, Karen Alejandra Méndez-Lara, David Santos, Núria Cabrerizo, Lucía Baila-Rueda, Jari Metso, Ana Cenarro, Eva Pardina, Albert Lecube, Matti Jauhiainen, Julia Peinado-Onsurbe, Joan Carles Escolà-Gil, Francisco Blanco-Vaca, Josep Julve
Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28549851/identification-of-pathway-based-prognostic-gene-signatures-in-patients-with-multiple-myeloma
#18
Mohamad Zamani-Ahmadmahmudi, Shahreyar Dabiri, Nadia Nadimi
Molecular profiling is used to extract prognostic gene signatures in different cancers such as multiple myeloma (MM), which is the second most common hematological malignancy. In this study, we utilized gene expression profiles to find biological pathways that could efficiently predict survival time in patients with MM. Four data sets-namely GSE2658 (559 samples), GSE9782 (264 samples), GSE6477 (147 samples), and GSE57317 (55 samples)-were employed. GSE2658 was used as a training data set and the others as validation data sets...
May 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28528915/sphingosine-metabolism-as-a-therapeutic-target-in-cutaneous-melanoma
#19
REVIEW
Mohammed Dany
Melanoma is by far the most aggressive type of skin cancer with a poor prognosis in its advanced stages. Understanding the mechanisms involved in melanoma pathogenesis, response, and resistance to treatment has gained a lot of attention worldwide. Recently, the role of sphingolipid metabolism has been studied in cutaneous melanoma. Sphingolipids are bioactive lipid effector molecules involved in the regulation of various cellular signaling pathways such as inflammation, cancer cell proliferation, death, senescence, and metastasis...
May 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28506697/inflammation-and-hemostasis-in-older-octogenarians-implication-in-5-year-survival
#20
Judit Cubedo, Teresa Padró, Francesc Formiga, Assumpta Ferrer, Glòria Padrós, Esther Peña, Lina Badimon
Social changes and medical advances have increased longevity, but the conditions governing healthy vs unhealthy cardiovascular (CV) aging are not fully known. Factors beyond classical CV risk factors may have an important unrecognized value. We sought to identify proteins differentially expressed in healthy octogenarians (HOs) without a history of cardiovascular disease (CVD) and preserved functional and cognitive state compared with octogenarians with a history of CVD and cognitive decline (UHOs) using a systems biology approach, and investigated how these proteins relate to CV mortality at 5-year follow-up...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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